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Principal Investigator: MEGAN MORIARTY KELSEY
Organization: UNIVERSITY OF COLORADO DENVER
Fiscal Year: 2024
Award: $632,519
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
PROJECT SUMMARY
Obesity and subsequently type 2 diabetes (T2D) is increasingly common in adolescents, but the phenotype of
youth-onset T2D (YO-T2D) differs from adults. The NIDDK TODAY study we helped lead, demonstrated that
youth with T2D had a high (≈50%) and rapid failure rate on oral medications and faster need for insulin therapy
vs. adults treated for a similar duration in the ADOPT study. As further evidence, in our NIDDK RISE study,
where treatment responses in youth with impaired glucose tolerance (IGT) or newly diagnosed T2D were
directly compared to adults of similar BMI and initial glycemia, youth were twice as insulin resistant as adults
and had rapid deterioration of β-cell function and glycemic control compared to adults given the same
treatment with similar medication adherence. Finally in our HIP study, metformin did not improve insulin
sensitivity or secretion even when started early in puberty in normoglycemic youth with obesity, arguing for
innovative approaches. Of most concern, TODAY demonstrated an incidence of microvascular diabetes
complications ranging from 32-68% by a mean age of only 26.4±2.8 yrs, affecting individuals who should be at
their peak of productivity; complications more heavily affected those with minority race/ethnicity, raising
concerns related to health disparities. This unprecedented early morbidity and projected health care costs
mandate a focus on defining a) the ideal T2D diagnostic and/or screening criteria for youth b) pathophysiologic
distinctions between Y-T2D and adult-onset T2D c) how to prevent Y-T2D d) how to better treat Y-T2D once
present. Though some risk factors for developing Y-T2D (e.g. family history, obesity, etc.) are well-established,
only a small subset of these high-risk youth progress to T2D as adolescents. Thus, other causal components
need to be explored, such as adverse childhood experiences, stress, poverty, racism, sleep/circadian rhythm,
subtle differences within sedentary behavior, and the exact impact(s) of pubertal hormones. We propose to
enroll and follow longitudinally 3,540 diverse youth (236 from our site) at risk for developing T2D from urban
and rural locations who are early in puberty, and perform longitudinal assessments every 6 mo (HbA1c,
Taneda scale every 6 mo, OGTT/DXA/MRI, yearly) paired with additional sample storage to be analyzed once
a “critical mass” of youth with new-onset T2D is accumulated. We propose the following Specific Aims,
developed in collaboration with our stakeholders/community members from populations disproportionately
affected by T2D: 1. To assess patterns of change in metabolic and pubertal events, we will measure: glycemia,
insulin sensitivity/secretion, body composition, free living behaviors, and pubertal hormones, as well as bank
blood, stool, hair, and urine. 2. To assess psychosocial and psychological factors, we will measure stress,
discrimination, teasing, microaggressions, social status, access to care, depression/anxiety, and cortisol. 3. To
use the data collected in Aims 1 and 2 and apply unbiased data analysis methodology to identify biomarkers
for progression risk and develop a prediction model for who will develop Y-T2D.
Terms: <0-11 years old><21+ years old><Access to Care><Active Follow-up><Acute><Address><Adolescent><Adolescent Youth><Adult><Adult Human><Adult-Onset Diabetes Mellitus><Aeroseb-HC><Affect><Age><Amputation><Anxiety><Apoplexy><Approaches to prevention><Attention><BMI><BMI percentile><BMI z-score><Behavior><Behavior monitoring><Beta Cell><Bioelectrical Impedance><Biolectric Impedance><Biological><Blood Banks><Body Composition><Body mass index><Brain Vascular Accident><COVID-19><CV-19><Cardiac infarction><Cardiovascular><Cardiovascular Body System><Cardiovascular Organ System><Cardiovascular system><Cell Function><Cell Physiology><Cell Process><Cellular Function><Cellular Physiology><Cellular Process><Cerebral Stroke><Cerebrovascular Apoplexy><Cerebrovascular Stroke><Cetacort><Child><Child Youth><Children (0-21)><Chronic><Circadian Rhythms><Code><Coding System><Cognitive Discrimination><Collaborations><Communities><Complications of Diabetes Mellitus><Coronavirus Infectious Disease 2019><Cort-Dome><Cortef><Cortenema><Cortisol><Cortispray><Cortril><Creativeness><DEXA><DXA><Data><Data Analyses><Data Analysis><Dermacort><Deterioration><Development><Diabetes Complications><Diabetes Mellitus><Diabetes prevention><Diabetes-Related Complications><Diabetic Angiopathies><Diabetic Complications><Diabetic Vascular Complications><Diabetic Vascular Diseases><Diabetic Vascular Disorder><Diagnostic><Dimethylbiguanidine><Dimethylguanylguanidine><Discrimination><Disease><Disorder><Drugs><Dual-Energy X-Ray Absorptiometry><Dual-Energy Xray Absorptiometry><Ecological momentary assessment><Economic Income><Economical Income><Education><Educational aspects><Eldecort><Endocrine Gland Secretion><Enrollment><Ethnic Origin><Ethnicity><Event><Exposure to><Failure><Family><Feces><Future><Genetic><Gestational Diabetes><Gestational Diabetes Mellitus><Glycohemoglobin A><Glycosylated hemoglobin A><Goals><Hair><Hb A1><Hb A1a+b><Hb A1c><HbA1><HbA1c><Health Care Costs><Health Costs><Health Services Accessibility><Healthcare Costs><Heart Vascular><Hemoglobin A(1)><History><Hormones><Humulin R><Hydrocortisone><Hydrocortone><Hytone><Impoverished><In Situ><Incidence><Income><Individual><Insulin><Insulin Cell><Insulin Resistance><Insulin Secreting Cell><Intervention><Intervention Strategies><Intervention Studies><Interview><Ketosis-Resistant Diabetes Mellitus><Lead><Lipids><MR Imaging><MR Tomography><MRI><MRIs><Machine Learning><Magnetic Resonance Imaging><Maturity-Onset Diabetes Mellitus><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Medication><Mental Depression><Mental Health><Mental Hygiene><Metabolic><Metformin><Methodology><Monitor><Morbidity><Morbidity - disease rate><Myocardial Infarct><Myocardial Infarction><N,N-dimethyl-imidodicarbonimidic diamide><NIDDK><NIDDM><NMR Imaging><NMR Tomography><National Institute of Diabetes and Digestive and Kidney Diseases><Newly Diagnosed><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Novolin R><Nuclear Magnetic Resonance Imaging><Nutracort><Nyctohemeral Rhythm><OGTT><Obesity><Oral><Oral Glucose Tolerance Test><Outcome><Participant><Pattern><Pb element><Perception><Pharmaceutical Preparations><Phenotype><Physical activity><Physiologic><Physiological><Pilot Projects><Polysomnography><Population><Poverty><Pregnancy-Induced Diabetes><Preventative strategy><Prevention approach><Prevention strategy><Preventive strategy><Proctocort><Productivity><Psychological Factors><Psychological Health><Psychosocial Assessment and Care><Psychosocial Factor><Puberty><Questionnaires><Quetelet index><Race><Races><Recording of previous events><Regular Insulin><Risk><Risk Factors><Role><Rural Community><Sampling><Schedule><Sedentary behavior><Sedentary life-style><Site><Sleep><Sleep Monitoring><Sleep disturbances><Slow-Onset Diabetes Mellitus><Social status><Somnography><Stable Diabetes Mellitus><Standardization><Stress><Stroke><Subcellular Process><T2 DM><T2D><T2DM><Therapeutic Hormone><Time><Twenty-Four Hour Rhythm><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><Urban Community><Urine><Visit><Weight Gain><Weight Increase><Youth><Youth 10-21><Zeugmatography><aberrant sleep><access to health services><access to services><access to treatment><accessibility to health services><active followup><adiposity><adult onset diabetes><adulthood><adverse childhood events><adverse childhood experiences><ages><availability of services><behavioral monitoring><biologic><biomarker identification><body weight gain><body weight increase><brain attack><bully><bullying><cardiac infarct><cardiometabolic><cardiometabolism><care access><cerebral vascular accident><cerebrovascular accident><circadian process><circulatory system><co-morbid><co-morbidity><comorbidity><compare to control><comparison control><computer based prediction><coronary attack><coronary infarct><coronary infarction><coronavirus disease 2019><coronavirus disease-19><coronavirus infectious disease-19><corpulence><creativity><daily biorhythm><data interpretation><depression><design><designing><developmental><diabetes><disparity in health><disrupted sleep><disturbed sleep><drug adherence><drug compliance><drug/agent><early onset><enroll><follow up><follow-up><followed up><followup><glycemic control><health disparity><health equity promotion><health service access><health services availability><heart attack><heart infarct><heart infarction><heavy metal Pb><heavy metal lead><hemoglobin A1c><high risk><histories><identification of biomarkers><identification of new biomarkers><impaired glucose tolerance><impaired sleep><incomes><innovate><innovation><innovative><insulin resistant><insulin secretion><insulin sensitivity><insulin tolerance><intervention research><interventional research><interventional strategy><interventional study><interventions research><irregular sleep><juvenile><juvenile human><ketosis resistant diabetes><kids><machine based learning><marker identification><maturity onset diabetes><medication adherence><medication compliance><member><microaggression><microvascular complications of diabetes><novel><optimal therapies><optimal treatments><pandemic><pandemic disease><pilot study><polysomnographic><predictive modeling><pregnancy diabetes><prevent><preventing><progression risk><promote health equity><psychosocial><psychosocial assessment><psychosocial care><psychosocial studies><psychosocial support><psychosocial variables><racial><racial background><racial minority><racial origin><racism><recruit><response><response to therapy><response to treatment><rural area><rural location><rural region><screening><screenings><sedentary lifestyle><service availability><sleep disruption><sleep dysregulation><sleep measurement><sleep polysomnography><social><social position><social role><social standing><stool><stroked><strokes><therapeutic response><therapy response><treatment access><treatment response><treatment responsiveness><type 2 DM><type 2 diabetes in children><type II DM><type two diabetes><urban area><urban location><urban region><wt gain><youngster><β-cell><β-cells><βCell>